Portal de Periódicos da CAPES

Websites of note

2006; Wiley; Volume: 34; Issue: 5 Linguagem: Inglês

10.1002/bmb.2006.494034052667

1539-3429

Graham R. Parslow,

Drug-Induced Hepatotoxicity and Protection

This site combines educational and research material in a commendably professional manner. The site came to my attention as a recommendation from Furge and Guegenrisch in their recent paper about cytochrome P450 in this journal [1]. Cytochrome P450 is central to our very ability to survive in a milieu of synthetic chemicals and drugs (xenobiotics). I lecture on P450 in my science and medical courses and commend the excellent chapter in Devlin [2] as a key reference for students. Most textbooks give little more than footnote status to P450, so a supportive web site is most welcome to expand the information available to students. The section titled The History of Xenobiotic Metabolism contains the following background. “An examination of the fate of foreign compounds (xenobiotics) in biological systems is a natural outgrowth of man's curiosity about his environment and how it can affect his actions. While the majority of modern day studies concern the fate of drugs in man and animals there are extensive investigations on the fate of organic compounds in plants, animals and microorganisms. The term xenobiotic was coined to cover all organic compounds that were foreign to the organism under study. In some situations this is loosely defined to include naturally present compounds administered by alternate routes or at unnatural concentrations.” This section also provides a historical look at the development of xenobiotic metabolism presented as a calendar produced with commercial sponsorship. The 12 topics addressed are Woehler –the birth of metabolism; oxidation; sulfate conjugation; glucuronidation; methylation and acetylation; reduction; mercapturic acids; R. T. Williams as founder of the field of metabolism; B. B. Brodie and drug metabolism methodology; in vitro technology; cytochrome P450; and a look to the future. This progression of vignettes should appeal to students wanting an illustrated overview of xenobiotic metabolism. Washington University School of Medicine in St. Louis has a home page with interesting health information for a general readership. Nested below the home page is a site covering viruses for an academic audience. The sections include historical highlights, structural virology, solving the structure of icosahedral plant viruses, picornavirus structure, the influenza virus, hemagglutinin, the influenza virus neuraminidase, and issues of science and society. The well written sections are generally short, and there are links that elaborate on selected topics. The introductory timeline tabulates highlights in the chronology of virology in the 20th century, starting with the crystallization of tobacco mosaic virus in the 1930s. I feel obliged here to mention a former senior colleague, Rupert Best, who claimed priority for that crystallization but was never given the credit he asserted was his due (science is a story of people as well as facts). Under Solving the Structure of Icosahedral Plant Viruses, I found a link to an oral history of Michael Rossman, who solved the structure of southern bean mosaic virus. The origins of Rossman's work went back to the early 60s when he was at the Cavendish Laboratory in Cambridge, England working on the ideas of non-crystallographic symmetry. This link piqued my interest and turned out to be a gem with a transcript of an interview dated February 1999, recorded and edited by Sondra Schlesinger of Washington University in St. Louis. I have long admired Rossman for his work on dehydrogenases and his breakthrough realization that what dehydrogenases have in common is not homologous amino acid sequences but identical binding structures for nicotinamide nucleotides (the Rossman fold). The background to that work by Rossman is included in a constellation of other important work with stellar collaborators such as Max Perutz. The site is evolving, and comments are invited in the discussion section. The professional standard of the site is assisted by a grant from the Sloan Foundation that aims to foster a wholly new way of creating a historical record of recent major technical and scientific events. Other Sloan Foundation grants have supported the creation of over 30 web sites that you can link to from this site. Monsanto is an agricultural company with corporate headquarters located in St. Louis, MO. It is the best known of the companies that have introduced targeted genetic modifications of agricultural produce. The company home page has an abundance of self-promoting statements that are clearly aimed at refuting the many criticisms coming from what might be termed “the organic lobby.” These general statements include “We are focused on applying innovation and technology to assist farmers around the world to be more successful, helping them produce healthier foods, better animal feeds and more fibre, while also reducing agriculture's footprint on our environment.” A further general statement, included under archived news for 2006, is “Ten years after the first generation of genetically engineered (GE)1 varieties became commercially available, adoption of these varieties by U.S. farmers is widespread for major crops. Driven by farmers' expectations of higher yields, savings in management time, and lower pesticide costs, the adoption of corn, soybean, and cotton GE varieties has increased rapidly.” For educational use, there is a section, reached from a box at the top of the home page, titled Biotech Primer. The primer is divided into sections named The Basics of Plant Biotechnology, How Biotechnology Works, Why Biotechnology Matters, The Benefits of Biotechnology, Examples, A Brief Biotech Timeline, Frequently Asked Questions, and Glossary. The example used is cotton that is resistant to boll weevil attack, and the claims are that plantings of this cotton annually save 3.46 million pounds of raw material, conserve 1.48 million gallons of fuel oil, and eliminate 2.16 million pounds of industrial waste. In general terms, GE cotton reduces pesticide exposure risk, preserves beneficial insect populations, creates wildlife benefits, and gives cotton producers more time for family and community activities. The better informed critics wonder whether the lessons of Rachel Carson's Silent Spring [3] have really been learnt because smug assurances from scientific boffins accompanied horrendous damage to the global environment after the Second World War. This site is overwhelmingly an advocacy-for-GE site, but it has lots of news and semi-scientific links that would assist in reaching an informed assessment of the role of genetic engineering in agriculture. On balance, I am personally in favor of GE approaches, but the words of Albert Schweitzer, quoted by Carson [3], still need to be considered: “Man has lost the capacity to foresee and to forestall. He will end by destroying the Earth.” Plant Cell Biology on CD covers structure-function relationships in plant cells. It is suited to undergraduates, lecturers, and research workers. Plant Cell Biology is a two-CD set containing an Introduction to Plant Cells with in-depth coverage of mitochondria, plastids, and peroxisomes. The many images include 100 video sequences and animations plus transmission and scanning electron micrographs and confocal stereo images. A pair of stereo glasses is provided with each set of CDs. The total size is about 1.3 gigabytes. There is a built-in slide show generator to mount lecture presentations. Licenses are available for single users and for classroom situations (approximate respective costs are US$50 and US$260). The author is Emeritus Professor Brian Gunning from the Australian National University. There are 20 sample screens to inspect and, as you may expect, these are well chosen to put the product in a good light. I was taken back to undergraduate days by a micrograph of the chloroplasts of Spirogyra and impressed by a diagram showing the two competing reactions of ribulose 1,5-bisphosphate carboxylase oxygenase (RuBisco). It would seem to be an excellent resource for any lecturer covering the biochemistry of plants because the material is purposefully designed for slide presentation, thereby avoiding the high density of data and low readability of many textbook diagrams. It was an “aha!” moment when I was reading Roy Porter's ponderous medical history [4] and came across mention of Lydia Pinkham's Vegetable Compound, sold from 1873. There really was a Lily the Pink, as celebrated in song by the singing group Scaffold (see en.wikipedia.org/wiki/Lydia_Pinkham). Searching the net for more information on Lydia Pinkham led to discovery of the site given here. The Museum of Menstruation and Women's Health, abbreviated to MUM, offers the rich history of this subject and contemporary aspects of menstruation and selected topics of women's health. It transpires that Lydia Pinkham's Vegetable Compound was genuinely efficacious in some cases for ameliorating symptoms of menopause. It was marketed as a general panacea for all problems, particularly those of women. It contained 18% alcohol and was freely available during prohibition times, so some of the consumption was more than medicinal. Looking around the MUM site is an engaging browse. “Odd, funny and well researched” is how the site was described by The New York Times (an attribution to this review is given at the MUM site). The history of medicine by Roy Porter [4] relates how women were systematically excluded from mainstream medicine before the 1950s. Women and their issues were peripheral in the 19th century, and this neglect of half of the population made Lydia Pinkham's Vegetable Compound a great success in the U.S. Eventually, regulation through the Federal Drug Agency restricted the sales of Lily's type of concoction. I suspect that a thesis titled ”The rise and demise of Lily the Pink“ could amalgamate a lot of the scientific and cultural evolution of a century and a half. At the MUM site, you will find Lydia Pinkham's Vegetable Compound under patent medicines. Unfortunately, the information page has a large header that may hide the content, so be sure to page down from the first screen you see. Fig. 1 shows a graphic from the MUM site of a trade card advertising Lydia Pinkham's Vegetable Compound. The National Organization for Rare Disorders (NORD) is a federation of voluntary health organizations dedicated to helping people with rare diseases. NORD facilitates the identification and treatment of rare disorders through education and research. Some 6,000 rare diseases affect ∼25 million Americans, meaning that one in every 10 Americans will suffer a rare disease. This large constituency explains the large resources and professionalism of the NORD web site. NORD is a non-profit agency that was established in 1983 by patients and families who cooperated at that time to get the Orphan Drug Act passed. That act provided financial incentives to develop new treatments for rare diseases. Advocacy remains a function of NORD as evidenced by the successful passing of the Rare Disease Act of 2002 to encourage clinical research on diseases that might not otherwise be studied. There is a wealth of scientific understanding to be gleaned from rare genetic and metabolic conditions that alter normal functions. A singular strength of the original textbook by Stryer [5] was the featuring of glycogen storage diseases to illustrate how failure of any single enzymic step in connected pathways has drastic consequences. One of those diseases is Pompe's (lack of lysosomal α-1,4-glucosidase), so I was happy to read the following among the news items reported on the NORD site. ”The Food and Drug Administration has granted marketing approval (April 28, 2006) for Myozyme for the treatment of people with Pompe disease, a progressive and debilitating disorder. It is the first treatment approved for this disease. Dr. Steven Galson, director of FDA's Center for Drug Evaluation and Research, called the approval 'another example of the benefits of the Orphan Drug program.' Myozyme, an enzyme replacement product, is manufactured by Genzyme Corp. of Cambridge, Mass.“ Under the menu item Programs & Services, there is a list of free booklets that can be viewed, in whole or in part, over the web. The six booklets are The Pediatrician's Guide to Tyrosinemia Type I, The Pediatrician's Guide to Ornithine Transcarbamylase Deficiency and other Urea Cycle Disorders, The Physician's Guide to Primary Lateral Sclerosis, The Physician's Guide to Pompe's Disease, The Physician's Guide to Multiple System Atrophy, and The Physician's Guide to Hereditary Ataxia. Other choices include the Index of Rare Diseases and the Rare Disease Database, which can be searched for reports on ∼1,150 diseases. The searches produce abstracts that are serviceable introductions, but full reports are provided for a fee. I must confess to an addiction to this television series. I discovered House only recently when my students told me about it, and I obtained DVDs of the series. My medical students even asked whether they could be exempt from problem-based learning tutorials if they watched House. At best, it is inspirational and encourages the scientific pursuit of excellence in laboratory and medical practice. At worst, it is dangerously non-conformist and portrays unrealistic scenarios that would not be possible, or could not be tolerated, in the real world. My enjoyment comes in part from the circumstance that biochemistry is the underlying basis for the action with the scripts rewarding the viewer for knowledge and analytical ability. The promotional description from the web site states that House is a “new take on mystery, where the villain is a medical malady and the hero is an irreverent, controversial doctor who trusts no one, least of all his patients. Dr. Gregory House (Hugh Laurie) is devoid of bedside manner and wouldn't even talk to his patients if he could get away with it.” In looking through viewer reviews of the show at the web site, it is evident that House is very favorably received by both professional and general audiences. One commentator said that this show made him want to be a doctor. An episode titled Three Stories stood out in the ratings (it is episode 21, season 1, and first aired May 2005). The plot of Three Stories is that “House's ex-girlfriend Stacy Warner returns—not for House but to get help for her ailing husband. While House decides whether or not to take her case, Cuddy (the administrator) forces him to present a lecture to a class of medical students. As he weaves the stories of three patients who all present with a similar symptom, House gives a lecture the students will never forget.” This episode singularly annoyed and challenged me. Although medical associates have told me how unrealistic the show is in portraying medical practice, this was my turn for an unrealistic portrayal of lecturing in the heroic mold that only happens in fiction such as the films Educating Rita and Dead Poets Society. On balance, everyone should be challenged by this series. The Science Songwriters' Association was formed in 1999 for the purpose of promoting science through song. The members are musicians, scientists, and teachers and combinations thereof. My browsing through the offerings failed to reveal anything that was of personal appeal. However, the site does offer this challenging quotation from the physicist Richard Feynman. “Our poets do not write about it. Our artists do not try to portray this remarkable thing. I don't know why. Is no one inspired by our present picture of the universe? The value of science remains unsung by singers: you are reduced to hearing not a song or poem, but an evening lecture about it. This is not yet a scientific age.” This site is a repository for many genres of computer utility. In the Education section, under chemistry, the following four offerings have been selected for their good rating by reviewers. 1) Advanced Pathway Painter visualizes pathways providing the user with the ability to display any kind of quantitative data from gene and protein experiments directly within the pathways. The linking between the pathway items and the experimental data is done over the gene or protein names and their accession numbers. 2) SweetMollyGrace is a suite of freeware tools for rendering and animating molecules. It imports molecules in Protein Data Bank (PDB) or MOL XYZ format, generates high quality images of molecules using ray tracing tools (Povray and Raster3D), and makes four kinds of animation by rotation around axes. It saves animation in AVI, MPEG, GIF, MOV, and FLIC formats. 3) ACD/ChemSketch, a “global smash hit,” facilitates chemical drawing and graphics. The program provides templates or allows for freehand drawing of structures. The program calculates molecular weight and formulae and estimates density, refractive index, and molar volume. You can generate the systematic International Union of Pure and Applied Chemistry (IUPAC) name for small molecules. 4) AcaClone pDRAW32 renders and analyzes sequences for DNA cloning, restriction analysis, and primer site analysis. pDRAW32 is still in beta testing, and you are asked to report any bugs you may encounter. While visiting the Freewarehome home page, if you find that you are the prize winner of the hour in a banner ad or pop-up screen, ignore it unless you want to buy a time-share holiday. An advertisement for Lydia Pinkham's Vegetable Compound from the MUM site. Shown is a trade card with a picture of the Brooklyn Bridge from the late 19th century, used to advertise the patent medicine Lydia Pinkham's Vegetable Compound.